“Postmenopausal syndrome” refers to various pathologic conditions caused by the decline in estrogen secretion when women are in or have completed physiological metamorphosis, namely, menopause. It is mainly represented in osteoporosis, estrogen-dependent cancers (breast cancer, endometrial cancer and ovarian cancer), cardiovascular diseases and senile dementia, etc.
Osteoporosis is a systemic bone disease characterized in the low bone mass and the degeneration of bone tissue microstructure. The population suffering from the osteoporosis in China currently accounts for about 7% of the total population, in which, the number of female patients with osteoporosis is 4 times of that of male patients, most common in postmenopausal women. The osteoporosis is not only harmful to individuals, but also causes a large number of economic losses due to its long disease course and its sequelae resulting in that patients need long-term treatment and nursing care and more so in older patients. In addition, although it is generally believed that osteoporosis is not life-threatening, 20% to 30% mortality rate in elderly women is related to hip fractures and this mortality rate is, in large part, related to the postmenopausal osteoporosis. The treatment method which is widely accepted for postmenopausal osteoporosis today is estrogen replacement treatment, which, although can relieve symptoms, will also produce some significant side effects, mainly in that the estrogen simulates endometrial hyperplasia, sometimes resulting n the cyclical bleeding, and even the occurrence of endometrial cancer and breast cancer. Raloxifene is the first selective estrogen receptor modulator that is approved to be used in the treatment of osteoporosis, but it has the tendency to increase hot flash and uterine hemorrhage.
Uterine fiber deterioration (uterine fibroids) is an ancient but still existing clinical problem up to now, including uterine fibroids, metrauxe, hysteromyoma, myometrial hypertrophy, uterine fiber deterioration and fiber uterine tumors. Generally speaking, uterine fiber deterioration is a pathologic condition in that the fibrous tissue improperly deposits on the uterine wall. This is one of the reasons for dysmenorrhea and infertility in women. The exact cause of uterine fiber deterioration is still poorly understood, but there are evidences indicating that it is caused by an unsuitable response of fibrous tissue to hormone. The surgery is the most conventional method to treat uterine fiber deterioration, which is expensive and sometimes induces complications such as abdominal adhesion and infection. For some patients, the initial surgery is only a temporary treatment and the fibers will regrow. In these cases, the hysterectomy can effectively terminate the growth of fibers, but patients also lose fertility. This disease can also be treated by administrating antagonists of gonadotropin-releasing hormone, but the use of them is restricted to the risk of causing osteoporosis. Thus, a new method is required for the treatment of uterine fiber deterioration.
Breast cancer is another common disease in elderly women and its main chemotherapy is to use selective estrogen receptor modulators, of which tamoxifen is in the highest flight. However, tamoxifen has significant drawbacks in that it shows the nature of estrogen agonist in the uterus and has a stimulating effect on the uterine cancer cells.
Brain tumor diseases refer to intracranial tumors, which can be divided, according to the lesion sources, into primary brain tumors and metastatic tumors metastasized from lung tumors. Glioma is the most common intracranial malignancy, accounting for more than 50% of the primary tumors of the nervous system. It is a type of malignancies with great hazard, high morbidity and high mortality rate. At present, surgery is the preferred treatment of glioma. However, the glioma mostly shows infiltrative growth and it is difficult to do total resection in surgery, so the glioma will generally recrudesce soon after surgery. Chemotherapy is an important supplement to the treatment of glioma and the main drug is nitrosourea, alone, or in combination with other drugs. However, the effect of chemotherapy on glioma is not satisfied enough for at least two reasons. One is that the existence of blood brain barrier prevents anticancer drugs to enter into the brain and the other is that quite a part of tumors are resistant to anticancer drugs. It has been found in studies that the overexpressed protein kinase C (PKC) in human glioma is related to the occurrence and development of tumors. As an estrogen receptor modulator, tamoxifen is mainly used to treat breast cancer in clinic. However, it is also a broad spectrum PKC inhibitor which prevents the growth of cancer cells by inhibiting PKC activity. Therefore, it is considered as a broad-spectrum antineoplastic drug.
Lung cancer is also one of the most common malignancies, the mortality rate of which is the first in the world. From the perspective of clinical features, it is inclined to divide, internationally, the lung cancer into the small cell lung cancer and the non-small cell lung cancer. The non-small cell lung cancer accounts for more than 85% of lung cancers. With the development and application of chemotherapeutics and molecular targeted drugs as well as the development of multidisciplinary treatment model of lung cancer in recent years, the overall 5-year survival rate of lung cancer has been significantly improved. Platinum-based combined chemotherapy remains the standard first-line chemotherapy of the advanced non-small cell lung cancer. The application of pemetrexed and docetaxel in clinic has improved the survival rate, remission rate and life quality of patients suffering from lung cancers to some extent. American Society of Clinical Oncology (ASCO) pointed out, in Annual Progress Report (2008), that the first-line treatment of the non-small cell lung cancer by cetuximab in combination with chemotherapy can improve 21% survival rate of patents suffering from the advanced lung cancer. At present, the tumor biotherapy with the representative of molecular target therapeutic agents has brought a new hope to the treatment of lung cancer, and in the future, the research on the treatment of lung cancer should focus on the biomolecular targeted therapy in combination with the chemotherapy or the multi-targeted therapy in combination with the chemotherapy.
Tumor metastasis is a successional multi-step active process. Tumor cells reach another position or multiple positions along certain channels from the primary tumor through the lymphatic channel, blood and cavity, forming a new metastasis. There are mainly four approaches of tumor metastasis: local spreading—constantly infiltrating the surrounding tissue, known as direct spreading of malignancy; lymphatic infiltration—metastasis from a local lymphatic to the whole lymphatic; hematogenous metastasis—metastasis to tissues and organs rich in blood flow along with the blood flow; cavity planting—implantation metastasis of tumor cells to the chest, the abdomen and the spinal cord cavity. The lymphatic infiltration and hematogenous metastasis are more common in these four ways. The recurrence rate of 1 year after the tumor surgery in China is up to 60% currently and more than 80% patients die of tumor recurrence and metastasis. It can be seen that the inhibition of metastasis and recurrence is as important as the treatment of the tumor.